S112: THE EFFECT OF IMMUNOGLOBULIN PROPHYLAXIS ON INFECTIOUS MORBIDITY IN PEDIATRIC PATIENTS WITH ACUTE LYMPHOBLASTIC LEUKEMIA: RESULTS OF A RANDOMIZED CONTROLLED TRIAL
Authors: Kirsten Thus, Hester de Groot-Kruseman, Pauline Winkler-Seinstra, Heidi Seegers, Marta Fiocco, Cornelis van Tilburg, Rob Pieters, Marc Bierings
Journal: HemaSphere (2023)

Background: Infections lead to substantial morbidity during treatment of acute lymphoblastic leukemia (ALL). During ALL treatment, the adaptive immune system gets severely affected, leading to, amongst other things, declining serum immunoglobulin (IgG) levels. Theoretically, one may partially overcome the infection risk by supplementing the low IgG levels with intravenous immunoglobulins (IVIG). Aims: The aim of this trial was to investigate whether IVIG prophylaxis in pediatric patients with medium risk (MR) ALL can prevent admissions for fever. Methods: This randomized controlled trial was a subtrial of the national Dutch multicenter ALL study (DCOG ALL-11). Patients aged 1-19 years with MR ALL were randomized into either IVIG prophylaxis (receiving 0.7 g/kg IVIG every three weeks) or control group (receiving standard of care). The primary endpoint was number of admissions for fever. Secondary endpoints were antibiotic treatments during admission for fever, adaptation of chemotherapy after admission for fever, ICU admissions, relapse, event-free survival (EFS), overall survival (OS). To account for possible correlations between episodes within the same patient, a generalized estimating equation (GEE) was fitted for admissions for fever, therapeutic antibiotics, chemotherapy adaptations and ICU admissions. Age was included in the GEE models as a factor. Results: Between October 2012 until March 2019, 165 patients were enrolled; 82 (50%) patients were randomly assigned to IVIG prophylaxis and 83 (50%) to the control arm. There were no significant differences in baseline characteristics. In the IVIG prophylaxis group there were 198 admissions for fever versus 265 in the control group (p=0.055, based on GEE models adjusted for age, Figure). During maintenance treatment of ALL, IVIG prophylaxis was associated with a significantly reduced number of admissions for fever (N=99 versus 163, for IVIG prophylaxis versus control group, respectively, p=0.005, Figure), resulting in significantly less antibiotic treatments (N=78 versus 136, for IVIG prophylaxis versus control, respectively, p=0.011, Figure). IVIG prophylaxis was associated with a significant reduction in admissions for fever with negative blood cultures compared to the control group (N=108 versus 198, for IVIG prophylaxis versus control, respectively, p=0.009, Figure), especially during maintenance treatment of ALL (N=52 versus N=124, for IVIG prophylaxis versus control, respectively, p=0.014, Figure). Next, IVIG prophylaxis led to a significant decrease of chemotherapy adaptations after admission for fever (N=119 versus 181, for IVIG prophylaxis versus control, respectively, p=0.024, Figure), especially during maintenance treatment of ALL as well (N=72 versus 132, for IVIG prophylaxis versus control, respectively, p=0.004, Figure). There was a low number of relapse in this study and IVIG prophylaxis did not significantly impact 5-year incidence of relapse, EFS or OS. Figure: Admissions for fever; with negative blood cultures, courses of antibiotics, or chemotherapy adaptation for IVIG and control group*: p<0.05, **: p<0.01 during entire ALL treatment; #: p<0.05, ##: p<0.01 during maintenance phase of ALL treatment separately. Summary/Conclusion: In pediatric patients with MR ALL, IVIG prophylaxis is associated with a significantly reduced number of admissions for fever (with a negative blood culture) during maintenance treatment, resulting in less antibiotic treatments and a decreased number of chemotherapy adaptations. Future studies should aim at identifying which patients benefit most from IVIG prophylaxis. Keywords: Pediatric, Randomized, Immunoglobulin, Acute lymphoblastic leukemia